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目的:探讨辛伐他汀对急性肺损伤大鼠囊性纤维化跨膜传导调节体(CFTR氯离子通道)的影响及其对减轻急性肺损伤的作用。方法:40只雄性SD大鼠随机分为空白组、模型组、辛伐他汀低剂量组(20 mg/kg)、辛伐他汀中剂量组(40 mg/kg)、辛伐他汀高剂量组(80 mg/kg);气道内滴注脂多糖(10 mg/kg)制备急性肺损伤模型。进行肺湿/干重比、肺泡灌洗液蛋白检测,HE染色观察肺组织的病理变化;实时荧光定量PCR检测肺组织匀浆CFTR mRNA表达。结果:结果显示,模型组的肺湿干重比,肺泡灌洗液蛋白较空白组高(P<0.05),病理示肺泡膈增厚,大量炎性细胞浸润,肺泡腔内可见红细胞及血肿,提示模型复制成功。辛伐他汀低剂量组的肺湿/干重比、肺泡灌洗液蛋白与模型组相比无明显差异,病理可见肺损伤较重,与模型组相比无改善;CFTR mRNA表达与模型组相比稍高但无明显差异(P<0.05)。辛伐他汀中高剂量组中肺湿/干重比、肺泡灌洗液蛋白与模型组相比有所降低,肺组织CFTRmRNA表达较模型组明显增加(P<0.05),但中高剂量组之间无明显差异(P>0.05);病理可见肺泡膈增厚,极少见炎性细胞浸润及透明膜,肺泡腔内未见明显出血和水肿,肺损伤程度较模型组减轻。结论:中高剂量的辛伐他汀(>40 mg/kg)对急性肺损伤有一定保护作用,并上调CFTR的表达。
Objective: To investigate the effect of simvastatin on cystic fibrosis transmembrane conductance regulator (CFTR chloride channel) in acute lung injury and its effect on reducing acute lung injury. Methods: Forty male Sprague-Dawley rats were randomly divided into three groups: the blank group, the model group, the simvastatin low dose group (20 mg / kg), the simvastatin medium dose group (40 mg / kg), the simvastatin high dose group 80 mg / kg). Acute lung injury model was induced by intratracheal instillation of lipopolysaccharide (10 mg / kg). Lung wet / dry weight ratio, alveolar lavage fluid protein detection, HE staining to observe the pathological changes of lung tissue; Real-time fluorescence quantitative PCR detection of lung tissue homogenate CFTR mRNA expression. Results: The results showed that the lung wet / dry weight ratio and the protein of BALF in the model group were higher than those in the blank group (P <0.05). The pathological changes showed thickening of the alveolar septum, infiltration of inflammatory cells, red blood cells and hematoma in the alveolar cavity, Prompt model copied successfully. Compared with the model group, the lung wet / dry weight ratio and the protein of BALF in the simvastatin low dose group showed no significant difference, and the lung injury was heavier in the pathological group than in the model group. The expression of CFTR mRNA in the model group Slightly higher than no significant difference (P <0.05). Compared with the model group, the lung wet / dry weight ratio and pulmonary alveolar lavage fluid protein in simvastatin group were significantly lower than those in model group (P <0.05). However, the expression of CFTR mRNA in lung tissue increased significantly (P <0.05) Significant difference (P> 0.05); pathological thickening of the alveolar septum, rare infiltration of inflammatory cells and transparent membrane, no significant alveolar hemorrhage and edema, lung injury than the model group. CONCLUSIONS: Middle and high dose of simvastatin (> 40 mg / kg) has a protective effect on acute lung injury and up-regulates the expression of CFTR.